Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jan 18;82(2):323–329. doi: 10.1054/bjoc.1999.0922

Loss of heterozygosity at 7p in Wilms' tumour development

R M Powlesland 1, A K Charles 2, K T A Malik 1, P A Reynolds 1, S Pires 3, M Boavida 3, K W Brown 1
PMCID: PMC2363297  PMID: 10646884

Abstract

Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaign

Keywords: loss of heterozygosity, chromosome 7, Wilms' tumour, tumour suppressor gene

Full Text

The Full Text of this article is available as a PDF (118.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Austruy E., Candon S., Henry I., Gyapay G., Tournade M. F., Mannens M., Callen D., Junien C., Jeanpierre C. Characterization of regions of chromosomes 12 and 16 involved in nephroblastoma tumorigenesis. Genes Chromosomes Cancer. 1995 Dec;14(4):285–294. doi: 10.1002/gcc.2870140407. [DOI] [PubMed] [Google Scholar]
  2. Beckwith J. B., Kiviat N. B., Bonadio J. F. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor. Pediatr Pathol. 1990;10(1-2):1–36. doi: 10.3109/15513819009067094. [DOI] [PubMed] [Google Scholar]
  3. Brown K. W., Villar A. J., Bickmore W., Clayton-Smith J., Catchpoole D., Maher E. R., Reik W. Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway. Hum Mol Genet. 1996 Dec;5(12):2027–2032. doi: 10.1093/hmg/5.12.2027. [DOI] [PubMed] [Google Scholar]
  4. Call K. M., Glaser T., Ito C. Y., Buckler A. J., Pelletier J., Haber D. A., Rose E. A., Kral A., Yeger H., Lewis W. H. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. doi: 10.1016/0092-8674(90)90601-a. [DOI] [PubMed] [Google Scholar]
  5. Charles A. K., Brown K. W., Berry P. J. Microdissecting the genetic events in nephrogenic rests and Wilms' tumor development. Am J Pathol. 1998 Sep;153(3):991–1000. doi: 10.1016/S0002-9440(10)65641-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Charles A. K., Vujanić G. M., Berry P. J. Renal tumours of childhood. Histopathology. 1998 Apr;32(4):293–309. doi: 10.1046/j.1365-2559.1998.00344.x. [DOI] [PubMed] [Google Scholar]
  7. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  8. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  9. Fletcher J. A., Renshaw A. A. Isochromosome 7q in adult Wilms' tumor. Cancer Genet Cytogenet. 1996 Feb;86(2):168–169. doi: 10.1016/0165-4608(95)00172-7. [DOI] [PubMed] [Google Scholar]
  10. Francke U., Holmes L. B., Atkins L., Riccardi V. M. Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet. 1979;24(3):185–192. doi: 10.1159/000131375. [DOI] [PubMed] [Google Scholar]
  11. Gessler M., Poustka A., Cavenee W., Neve R. L., Orkin S. H., Bruns G. A. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. doi: 10.1038/343774a0. [DOI] [PubMed] [Google Scholar]
  12. Grundy P. E., Telzerow P. E., Breslow N., Moksness J., Huff V., Paterson M. C. Loss of heterozygosity for chromosomes 16q and 1p in Wilms' tumors predicts an adverse outcome. Cancer Res. 1994 May 1;54(9):2331–2333. [PubMed] [Google Scholar]
  13. Grundy R. G., Pritchard J., Scambler P., Cowell J. K. Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour. Oncogene. 1998 Jul 23;17(3):395–400. doi: 10.1038/sj.onc.1201927. [DOI] [PubMed] [Google Scholar]
  14. Hastie N. D. The genetics of Wilms' tumor--a case of disrupted development. Annu Rev Genet. 1994;28:523–558. doi: 10.1146/annurev.ge.28.120194.002515. [DOI] [PubMed] [Google Scholar]
  15. Hearne C. M., Ghosh S., Todd J. A. Microsatellites for linkage analysis of genetic traits. Trends Genet. 1992 Aug;8(8):288–294. doi: 10.1016/0168-9525(92)90256-4. [DOI] [PubMed] [Google Scholar]
  16. Hewitt M., Lunt P. W., Oakhill A. Wilms' tumour and a de novo (1;7) translocation in a child with bilateral radial aplasia. J Med Genet. 1991 Jun;28(6):411–412. doi: 10.1136/jmg.28.6.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Huang A., Campbell C. E., Bonetta L., McAndrews-Hill M. S., Chilton-MacNeill S., Coppes M. J., Law D. J., Feinberg A. P., Yeger H., Williams B. R. Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor. Science. 1990 Nov 16;250(4983):991–994. doi: 10.1126/science.2173145. [DOI] [PubMed] [Google Scholar]
  18. Huff V., Saunders G. F. Wilms tumor genes. Biochim Biophys Acta. 1993 Dec 23;1155(3):295–306. doi: 10.1016/0304-419x(93)90011-z. [DOI] [PubMed] [Google Scholar]
  19. Kaneko Y., Homma C., Maseki N., Sakurai M., Hata J. Correlation of chromosome abnormalities with histological and clinical features in Wilms' and other childhood renal tumors. Cancer Res. 1991 Nov 1;51(21):5937–5942. [PubMed] [Google Scholar]
  20. Keen T. J., Inglehearn C. F., Green E. D., Cunningham A. F., Patel R. J., Peacock R. E., Gerken S., White R., Weissenbach J., Bhattacharya S. S. A YAC contig spanning the dominant retinitis pigmentosa locus (RP9) on chromosome 7p. Genomics. 1995 Aug 10;28(3):383–388. doi: 10.1006/geno.1995.1165. [DOI] [PubMed] [Google Scholar]
  21. Knudson A. G., Jr, Strong L. C. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. 1972 Feb;48(2):313–324. [PubMed] [Google Scholar]
  22. Lahoti C., Thorner P., Malkin D., Yeger H. Immunohistochemical detection of p53 in Wilms' tumors correlates with unfavorable outcome. Am J Pathol. 1996 May;148(5):1577–1589. [PMC free article] [PubMed] [Google Scholar]
  23. Löbbert R. W., Klemm G., Grüttner H. P., Harms D., Winterpacht A., Zabel B. U. Novel WT1 mutation, 11p LOH, and t(7;12) (p22;q22) chromosomal translocation identified in a Wilms' tumor case. Genes Chromosomes Cancer. 1998 Apr;21(4):347–350. doi: 10.1002/(sici)1098-2264(199804)21:4<347::aid-gcc9>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  24. Maitland N. J., Cox M. F., Lynas C., Prime S. S., Meanwell C. A., Scully C. Detection of human papillomavirus DNA in biopsies of human oral tissue. Br J Cancer. 1987 Sep;56(3):245–250. doi: 10.1038/bjc.1987.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Malkin D., Sexsmith E., Yeger H., Williams B. R., Coppes M. J. Mutations of the p53 tumor suppressor gene occur infrequently in Wilms' tumor. Cancer Res. 1994 Apr 15;54(8):2077–2079. [PubMed] [Google Scholar]
  26. Maw M. A., Grundy P. E., Millow L. J., Eccles M. R., Dunn R. S., Smith P. J., Feinberg A. P., Law D. J., Paterson M. C., Telzerow P. E. A third Wilms' tumor locus on chromosome 16q. Cancer Res. 1992 Jun 1;52(11):3094–3098. [PubMed] [Google Scholar]
  27. McDonald J. M., Douglass E. C., Fisher R., Geiser C. F., Krill C. E., Strong L. C., Virshup D., Huff V. Linkage of familial Wilms' tumor predisposition to chromosome 19 and a two-locus model for the etiology of familial tumors. Cancer Res. 1998 Apr 1;58(7):1387–1390. [PubMed] [Google Scholar]
  28. Mellersh C., Sampson J. Simplifying detection of microsatellite length polymorphisms. Biotechniques. 1993 Oct;15(4):582–584. [PubMed] [Google Scholar]
  29. Miozzo M., Perotti D., Minoletti F., Mondini P., Pilotti S., Luksch R., Fossati-Bellani F., Pierotti M. A., Sozzi G., Radice P. Mapping of a putative tumor suppressor locus to proximal 7p in Wilms tumors. Genomics. 1996 Nov 1;37(3):310–315. doi: 10.1006/geno.1996.0565. [DOI] [PubMed] [Google Scholar]
  30. Miyagawa K., Kent J., Moore A., Charlieu J. P., Little M. H., Williamson K. A., Kelsey A., Brown K. W., Hassam S., Briner J. Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour. Nat Genet. 1998 Jan;18(1):15–17. doi: 10.1038/ng0198-15. [DOI] [PubMed] [Google Scholar]
  31. Ogawa O., Eccles M. R., Szeto J., McNoe L. A., Yun K., Maw M. A., Smith P. J., Reeve A. E. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature. 1993 Apr 22;362(6422):749–751. doi: 10.1038/362749a0. [DOI] [PubMed] [Google Scholar]
  32. Park S., Bernard A., Bove K. E., Sens D. A., Hazen-Martin D. J., Garvin A. J., Haber D. A. Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour. Nat Genet. 1993 Dec;5(4):363–367. doi: 10.1038/ng1293-363. [DOI] [PubMed] [Google Scholar]
  33. Peier A. M., Meloni A. M., Erling M. A., Sandberg A. A. Involvement of chromosome 7 in Wilms tumor. Cancer Genet Cytogenet. 1995 Jan;79(1):92–94. doi: 10.1016/0165-4608(94)00110-w. [DOI] [PubMed] [Google Scholar]
  34. Ping A. J., Reeve A. E., Law D. J., Young M. R., Boehnke M., Feinberg A. P. Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet. 1989 May;44(5):720–723. [PMC free article] [PubMed] [Google Scholar]
  35. Radice P., Perotti D., De Benedetti V., Mondini P., Radice M. T., Pilotti S., Luksch R., Fossati Bellani F., Pierotti M. A. Allelotyping in Wilms tumors identifies a putative third tumor suppressor gene on chromosome 11. Genomics. 1995 Jun 10;27(3):497–501. doi: 10.1006/geno.1995.1082. [DOI] [PubMed] [Google Scholar]
  36. Rahman N., Arbour L., Tonin P., Renshaw J., Pelletier J., Baruchel S., Pritchard-Jones K., Stratton M. R., Narod S. A. Evidence for a familial Wilms' tumour gene (FWT1) on chromosome 17q12-q21. Nat Genet. 1996 Aug;13(4):461–463. doi: 10.1038/ng0896-461. [DOI] [PubMed] [Google Scholar]
  37. Rainier S., Johnson L. A., Dobry C. J., Ping A. J., Grundy P. E., Feinberg A. P. Relaxation of imprinted genes in human cancer. Nature. 1993 Apr 22;362(6422):747–749. doi: 10.1038/362747a0. [DOI] [PubMed] [Google Scholar]
  38. Reeve A. E., Sih S. A., Raizis A. M., Feinberg A. P. Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol. 1989 Apr;9(4):1799–1803. doi: 10.1128/mcb.9.4.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Reik W., Maher E. R. Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome. Trends Genet. 1997 Aug;13(8):330–334. doi: 10.1016/s0168-9525(97)01200-6. [DOI] [PubMed] [Google Scholar]
  40. Reynolds P. A., Powlesland R. M., Keen T. J., Inglehearn C. F., Cunningham A. F., Green E. D., Brown K. W. Localization of a novel t(1;7) translocation associated with Wilms' tumor predisposition and skeletal abnormalities. Genes Chromosomes Cancer. 1996 Nov;17(3):151–155. doi: 10.1002/(SICI)1098-2264(199611)17:3<151::AID-GCC2>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
  41. Rivera H. Constitutional and acquired rearrangements of chromosome 7 in Wilms tumor. Cancer Genet Cytogenet. 1995 May;81(1):97–98. doi: 10.1016/s0165-4608(94)00199-5. [DOI] [PubMed] [Google Scholar]
  42. Rivera H., Ruiz C., García-Cruz D., Rolón A., Arroyo J., Cantú J. M. Constitutional mosaic t(2;7)(q33;p22) and other rearrangements in a girl with Wilms' tumor. Ann Genet. 1985;28(1):52–54. [PubMed] [Google Scholar]
  43. Sawyer J. R., Winkel E. W., Redman J. F., Roloson G. J. Translocation (7;7)(p13;q21) in a Wilms' tumor. Cancer Genet Cytogenet. 1993 Aug;69(1):57–59. doi: 10.1016/0165-4608(93)90114-2. [DOI] [PubMed] [Google Scholar]
  44. Sheffield V. C., Weber J. L., Buetow K. H., Murray J. C., Even D. A., Wiles K., Gastier J. M., Pulido J. C., Yandava C., Sunden S. L. A collection of tri- and tetranucleotide repeat markers used to generate high quality, high resolution human genome-wide linkage maps. Hum Mol Genet. 1995 Oct;4(10):1837–1844. doi: 10.1093/hmg/4.10.1837. [DOI] [PubMed] [Google Scholar]
  45. Sheng W. W., Soukup S., Bove K., Gotwals B., Lampkin B. Chromosome analysis of 31 Wilms' tumors. Cancer Res. 1990 May 1;50(9):2786–2793. [PubMed] [Google Scholar]
  46. Solis V., Pritchard J., Cowell J. K. Cytogenetic changes in Wilms' tumors. Cancer Genet Cytogenet. 1988 Sep;34(2):223–234. doi: 10.1016/0165-4608(88)90264-6. [DOI] [PubMed] [Google Scholar]
  47. Steenman M., Redeker B., de Meulemeester M., Wiesmeijer K., Voûte P. A., Westerveld A., Slater R., Mannens M. Comparative genomic hybridization analysis of Wilms tumors. Cytogenet Cell Genet. 1997;77(3-4):296–303. doi: 10.1159/000134602. [DOI] [PubMed] [Google Scholar]
  48. Weber J. L., Kwitek A. E., May P. E. Dinucleotide repeat polymorphisms at the D16S260, D16S261, D16S265, D16S266, and D16S267 loci. Nucleic Acids Res. 1990 Jul 11;18(13):4034–4034. doi: 10.1093/nar/18.13.4034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wilmore H. P., White G. F., Howell R. T., Brown K. W. Germline and somatic abnormalities of chromosome 7 in Wilms' tumor. Cancer Genet Cytogenet. 1994 Oct 15;77(2):93–98. doi: 10.1016/0165-4608(94)90221-6. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES